Population Disparities in Mental Health: Insights From Cultural Neuroscience

Abstract

By 2050, nearly 1 in 5 Americans (19%) will be an immigrant, including Hispanics, Blacks, and Asians, compared to the 1 in 8 (12%) in 2005. They will vary in the extent to which they are at risk for mental health disorders. Given this increase in cultural diversity within the United States and costly population health disparities across cultural groups, it is essential to develop a more comprehensive understanding of how culture affects basic psychological and biological mechanisms. We examine these basic mechanisms that underlie population disparities in mental health through cultural neuroscience. We discuss the challenges to and opportunities for cultural neuroscience research to determine sociocultural and biological factors that confer risk for and resilience to mental health disorders across the globe.

Mental health disorders make up the majority of disease around the world and pose a significant global financial burden in treatment costs annually.^1,2 The Joint Center for Political and Economic Studies² estimated that eliminating racial/ethnic minority health disparities would have reduced indirect costs in the United States associated with illness and premature death by more than $1 trillion between 2003 and 2006 alone.² A key challenge facing global mental health is to understand the factors affecting etiology and treatment of mental health disorders, as well as the mechanisms underlying disparities in mental health disorders across nations. Over the past 2 decades, much progress has been made in identifying the key social and biological mechanisms underlying most common mental health disorders, including anxiety, depression, schizophrenia, addiction, Alzheimer’s disease, and posttraumatic stress disorder.³ Currently, genetic, neuroscience, and behavioral science research indicates that underlying all of these complex phenotypes is a complex interplay of genetic and environmental factors that shape neural, psychological, and behavioral endophenotypes that ultimately affect risk for and resilience to mental health disorders.^3,4

Most advances in mental health research, particularly in the behavioral and brain sciences, have been conducted in Western industrialized nations, geographic regions with the technological, economic, and intellectual resources to support high quality scientific work.^5,6 Such researcher biases studying the etiology of mental health disorders would not be worrisome if the mechanisms underlying such disorders were largely universal or invariant to environmental factors that vary across geographic regions. However, research in cultural neuroscience shows that key environmental features, including cultural, geographic, and socioeconomic factors modulate genetic, neural, and behavioral mechanisms underlying mental health disorders.⁶ Furthermore, sociocultural variation in biological mechanisms underlying mental health disorders may explain, in part, population disparities in mental health across ethnic groups within and across nations. Given that our current knowledge of biological mechanisms underlying mental health disorders is restricted to Western industrialized nations,^5,6 increased awareness of researcher biases and practical measures that increase research in non-Western industrialized nations or low-to-middle income countries are necessary to fully develop understanding of the etiology of and treatment of mental health disorders around the world.

We provide a summary of existing research and suggestions for building research in cultural neuroscience, particularly across the developed or developing world or the North–South divide, to answer questions related to the social and biological mechanisms underlying mental health across the globe. Because of the lack of neuroscience studies conducted within non-Western regions, our comprehensive understanding of how the brain works predominantly relies on observations of neural structure and function from a restricted population. Furthermore, the environmental conditions that are unique within developing world, such as environmental pressures related to ecology and economic growth, may affect human brain evolution in ways not previously observed because of the lack of neuroscientific investigation within the non-Western world.

SOCIOCULTURAL FACTORS

Population health disparities refer to group differences in health outcomes or disease prevalence that are considered unfair or unjust because of the nature or origin of the difference.^7,8 Several sociocultural factors may contribute to population health disparities in health, including increased exposure to potential risk factors, such as environmental hazards, and reduced exposure to potential environmental buffers that confer resilience to disease and unequal access to adequate resources for effective treatment of disease.^7–9 For instance, racial/ethnic groups that are historically marginalized may experience greater risk of and exposure to negative stereotypes or associations^10,11 that either increase the likelihood that they experience reduced physical health and psychological well-being or hinder their ability to receive appropriate or equal access to effective health care treatment. Additionally, migratory groups and individuals who identify with multiple racial or ethnic groups, such as immigrants and refugees, may also be vulnerable to health disparities given their exposure to risks factors of more than 1 racial or ethnic group, including not only multiple racial or ethnic stereotypes, but also the acculturative stress or affective cost of integrating identities across more than 1 cultural or ethnic context.¹²

Individuals with lower, compared with higher, socioeconomic status (SES) are less likely to have access to quality health care and may experience greater risks to physical health¹³ because of poorer labor conditions.¹⁴ Individuals with lower SES may also be less likely to experience psychological well being because of increased psychological demands, such as a societal expectation that individuals of lower SES should adopt the perspective of those of higher SES.¹⁵ In addition, individuals with lower SES have fewer cognitive resources for learning, such as working memory and executive control,¹⁶ and less social resources, such as feeling in control of or of a choice in their environment.¹⁷

Effects of socioeconomic stratification on health conditions may be further perpetuated within and across generations because individuals tend to value the cultural beliefs and habits of people with similar SES,¹⁸ reducing the likelihood that a change will occur in psychological habits that may serve as risk factors for health disparities.^19,20 Racial identification may serve as an important buffer in providing resilience for both physical and psychological diseases,^21,22 such as cardiovascular disease and psychological distress.

Sociocultural factors, such as racial/ethnic factors and SES, affect how health disparities interact, such that all racial/ethnic groups may not experience the same risk factors typically associated with lower SES conditions in a similar manner.¹⁴ For instance, the double jeopardy hypothesis states that for historically marginalized or discriminated groups, health disparities may be more pronounced because of their lower SES. This confers increased exposure to environmental hazards associated with poorer health conditions but reduced access to adequate health care treatment, in addition to increased racial or ethnic discrimination.^23,24 By contrast, the healthy immigrant hypothesis suggests that the risks to health for lower SES groups may be more applicable to native born or nonimmigrants compared with immigrant populations, possibly because of reduced access to distinct cultural knowledge and habits that confer resilience within multicultural contexts.^25,26 Taken together, these distinct sociocultural hypotheses suggest a greater understanding of sociocultural context, including effects of racial/ethnic identity and SES on health, are necessary for understanding the etiology of population health disparities within and across generations.

BIOLOGICAL FACTORS

Recent advances in population genetics indicate population structure in the human genome,^27,28 which contains biological variations that may contribute to health disparities.^29–31 Only approximately 3% to 5% of the human genome varies across major racial or ethnic groups; nevertheless, within this small fraction of the human genome, researchers are able to classify humans into approximately 6 major groups as a function of genetic distance.²⁷ Human genetic distance exhibits clines and clusters across geography, a result of both natural and neutral selection mechanisms.

There are multiple signatures for natural and neutral selection. Natural selection occurs when a novel allele is identically advantageous across space, when an allelic variant is advantageous in some geographic regions but not others, and when local selection pressures (e.g., presence of malaria) favor an advantageous allele either variably or uniformly across space. Geographic clines in allelic frequency can also occur through neutral selection mechanisms, such as isolation-by-distance and secondary contact.³² In isolation-by-distance, individuals mate with others who are from closer relative to distance populations, and as a consequence, populations closer in geographic distance will be closer in genetic distance relative to those farther apart. In secondary contact, neutral alleles may also show a cline pattern at the geographic zone of secondary contact between 2 populations who were previously separated. Allelic variation within functional loci of the genomic or specific functional polymorphisms may result as a function of both natural and neutral selection mechanisms. Allelic variation that occurs because of natural selection may be associated with specific functional adaptations that alter the likelihood of certain diseases, resulting in population disparities^28,30 in physical³² and psychological health.^33,34

Behavioral genetics, the study of behavioral traits associated with specific genes, has largely focused on empirical investigations within, rather than between, geographic regions, because of known genetic distance across populations as a function of geography. Considerable progress in behavioral genetics suggests that specific genes interact with environmental factors (G×E) in the etiology for complex yet common mental health diseases^4,35 across the globe.³ Several key candidate genes have been identified as playing a central role in interacting with specific environmental factors, leading to risk for or resilience to complex diseases, including the serotonin transporter gene (5-HTTLPR), catechol-O-methyltransferase, monamine oxidase A, and D4 dopamine receptor, among others.⁴ One of the most comprehensive models is a G×E model of depression,^36–40 which is currently considered the most common mental health disorder.³ The classic G×E model of depression asserts that individuals who carry 1 or 2 copies of the short (S) allele of the serotonin transporter gene (5-HTTLPR) are at greater risk of experiencing increased episodes of major depression with increasing prevalence of stressful life events, compared with individuals who carry the long (L) allele.^35,36 Convergent evidence for this classic G×E model exists across levels of analysis, including behavioral and neuroscience studies, as well as species, such as human and nonhuman primate studies. Numerous behavioral genetics studies have shown that compared with L allele carriers, S allele carriers are more likely to exhibit negative effects, such as neuroticism⁴⁰ and increased risk for depression when exposed to environmental stressors,^35,39 whereas neurogenetics studies have demonstrated increased amygdala response to emotional stimuli.^37,38,41,42

Notably, genetic distance may affect allelic frequency of the serotonin transporter gene, or population frequency of S allele carriers across the globe.^41,42 This biological factor may have contributed to the number of nonreplications of behavioral genetics findings that report a lack of a significant association of the S allele of the 5-HTTLPR gene and increased negative effects (e.g., neuroticism) from Eastern nations, including Japan,^43–47 Korea,^48–53 and Taiwan⁵⁴ (Table 1 ). Additionally, SES is an environmental factor known to interact with the serotonin transporter gene in central serotonergic responsivity (e.g., plasma prolactin), suggesting that SES may serve as an important moderating factor in G×E models of mental health.^55,56 Given that most behavioral and neurogenetics evidence is from studies conducted within specific geographic regions, specifically Western industrialized nations, more behavioral and neuroscience research is needed across geographic regions, specifically non-Western, industrialized nations and low-to-middle income countries, to assess the validity of this G×E model in a global context.

TABLE 1—

Summary of Behavioral Genetics Studies of Serotonin Transporter Gene and Negative Effects in East Asia

Reference	Nation	No. S/S	No. S/S	No. S/S	T-score S/S	T-score S/S	T-score S/S	P
Katsuragi et al.47	Japan	66	31	4	50.92	49.90	49.60	< .05
Murakami et al.48	Japan	124	55	10	51.18	47.74	47.74	< .05
Kumakiri et al.45	Japan	85	48	11	49.94	50.16	49.76	> .05
Nakamura et al.46	Japan	128	55	3	51.22	50.68	48.25	> .05
Umekage et al.49	Japan	161	70	13	50.15	49.90	48.59	.38
Ham et al.50	Korea	93	47	6	NA	NA	NA	> .05
Joo et al.51	Korea	95	54	9	51.14	50.59	52.78	.62
Kim et al.52	Korea	128	74	7	51.6	NA	50.5	.16
Kim et al.53	Korea	130	72	9	NA	NA	NA	> .05
Tsai et al.54	Taiwan	100	71	21	49.98	50.12	49.69	> .05

Note. S = short allele.

Epigenetics also plays a crucial role in our understanding of how sociocultural factors dynamically and reciprocally shape gene expression.^57–59 The extent to which people are integrated in social communities or isolated plays a profound role in gene expression.⁵⁸ People who are socially isolated show variable expression of genes that control human immune response, such as reciprocal shifts in the activity of pro- and anti-inflammatory transcription control pathways. Activity within plasmacytoid dentritic cells, monocytes, and B lymphocytes are altered in isolated or lonely individuals compared with nonisolated and socially integrated individuals.⁵⁸ Gene expression can also subsequently affect the psychological and neural mechanisms of social perception. Specifically, DNA methylation, an epigenetic mechanism in which cells control transcription by modifying chromatic structure, may play an important role in regulating neural and psychological processes. Recent neuroimaging evidence indicates, for the first time, that degree of methylation of the oxytocin receptor gene predicts neural response within the left superior temporal gyrus and the anterior cingulate gyrus in response to animate social movement compared with random social movement.⁵⁹ Hence, not only does social experience alter gene expression and subsequent health outcomes, but gene expression can also shape neural pathways of social cognition, possibly in response to the environmental demands of social experience.

CULTURAL NEUROSCIENCE AND POPULATION HEALTH DISPARITIES

Cultural neuroscience is a research field that examines how cultural values, practices, and beliefs shape and are shaped by neurobiological mechanisms across evolutionary, developmental, and situational timescales.^60–65 Researchers in cultural neuroscience integrate theory and methods from cultural psychology, neuroscience, and neurogenetics to examine the interaction of culture and genes in the production of endophenotypes, such as psychological and neural mechanisms, in complex human behavior. A chief goal of cultural neuroscience research is to increase understanding of population health disparities by elucidating a comprehensive, yet parsimonious, integrated model of human behavior that accurately describes the interaction of cultural, environmental, and biological factors in the etiology of complex human mental health (Figure 1). Understanding how and why populations may differ in their risk for or resilience to certain diseases is paramount to closing the gap in health disparities around the globe.

FIGURE 1—

Cultural neuroscience model of human behavior.

Note. Each factor in the cultural neuroscience model may be composed of a set of variables of each type (e.g., A1, A2 refers to distinct environmental variables; B1, B2 refers to distinct cultural variables).

Recent advances in cultural neuroscience demonstrate that cultural values, practices, and beliefs affect neural pathways known to contribute to the regulation and maintenance of mental health and psychological well-being. Cortical-limbic pathways, such as the amygdala and prefrontal cortex, are pivotal to the regulation of emotion and the maintenance of psychological homeostasis.^37,38 One of the most robust findings within cultural neuroscience is the modulation of neural response within the prefrontal regions as a function of cultural values, such as individualism and collectivism^66–68 (Table 2 ). People who endorse individualistic cultural values show greater medial prefrontal response when thinking about themselves in a general fashion (e.g., I am caring), whereas people who endorse collectivistic cultural values show greater neural response within the same region when thinking about themselves in a contextual fashion (e.g., When talking to my mother, I am caring)⁶⁶ across geographic regions, specifically the United States and Japan. Moreover, temporarily heightened awareness of individualistic or collectivistic values in bicultural individuals modulates neural response within cortical midline regions during culturally congruent self-judgments.⁶⁷ Even within geographic regions, culture affects the neural basis of social cognition. For instance, Europeans living in China show reduced medial frontal response when evaluating the traits of their mother compared with Chinese living in China.^68,69 Caucasians living in the United States also show dynamic effects of cultural priming on neural response within cortical midline regions both during explicit self-judgments,^69,71 and even when merely exposed to traits about the self in an implicit fashion.⁷⁰

TABLE 2—

Summary of Cultural Neuroscience Studies of Prefrontal-Amygdala Circuitry

Reference	Population	Region	Culture	Gene	Task
Brain region: prefrontal cortex
Zhu et al.68	13 CH, 13 EUR	East Asia	—	—	Self judgment
Chiao et al.66	12 CA, 12 JP	East Asia, North America	IND-COL	—	Self judgment
Chiao et al.67	30 AA	North America	IND-COL	—	Self judgment
Ray et al.69	18 US	North America	IND-COL	—	Self judgment
Harada et al.70	18 AA	North America	IND-COL	—	Self judgment
Wang et al.71	32 CH	East Asia	IND-COL	—	Self judgment
Mathur et al.72a	10 AA, 10 CA	North America	MEIM		Empathy
Brain regions: amygdala and hippocampus
Moriguchi et al.73	16 CA, 16 JP	East Asia	—	—	Emotion recognition
Chiao et al.74	10 CA, 10 JP	East Asia, North America	—	—	Emotion recognition
Lee and Ham75	55 KR	East Asia	—	5-HT(1A)	Emotion recognition
Derntl et al.76	24 EA, 24 EUR	Europe	—	—	Emotion recognition
Adams et al.77	16 JP, 18 CA	North America	—	—	Emotion recognition

Note. AA = African Americans; CA = Caucasian Americans; CH = Chinese; EA = East Asian; EUR = European; IND-COL = individualism-collectivism; JP = Japanese; KR = Korean; MEIM = Multiethnic identification measure; US = United States.

Several studies have also demonstrated the effect of culture on limbic neural circuitry, such as the amygdala. People living in distinct geographic regions, such as the United States and Japan, show increased amygdala response when viewing their own facial expressions of fear compared with facial expressions of fear in other cultures, suggesting a neural tuning within limbic regions to processing the social cues expressed by one’s own cultural group (Figure 2).^73,74 However, even within the same geographic region, cultural variation in amygdala response to emotional faces has been observed. Caucasians living in Japan have shown increased amygdala response to fear compared with happy faces when compared with native Japanese living in Japan.⁷⁶ By contrast, Asians living in Europe have shown increased amygdala response to emotional faces compared with Europeans living in Europe.⁷⁶ Cultural variation in amygdala response to emotional expressions may be due, in part, to duration in stay or familiarity with members of other cultural groups.⁷⁶ For Asians, longer durations of stay in Europe are associated with reduced amygdala response during emotion recognition.^78a Results from all of these cultural neuroscience studies, so far, show the effects of culture on neural response, even in absence of behavioral differences, demonstrating the importance of understanding not only how culture affects complex behavior, but also endophenotypes, such as brain function.⁶

FIGURE 2—

Response to emotional faces, by culture group, as shown in (a) scan showing left and right amygdala activity, (b) left amygdala activity by emotion, and (c) right amygdala by emotion.

Note. Culture modulates amygdala response to fear faces. Both White American and Japanese participants show greater bilateral amygdala response to fear faces of their own cultural group, compared with members of another cultural group.

Source. Adapted from Chiao et al.⁷⁴ Whiskers indicate 95% confidence intervals.

Sociocultural factors, such as racial identification and social dominance orientation, also play key roles in modulating neural processes that affect psychological well-being, including cortical and subcortical brain regions. Within the United States, Mathur et al.^72a and Derntl et al.⁷⁶ recently showed that race modulates neural responses within the medial prefrontal cortex when empathizing with members of one’s own racial group; specifically, African Americans show increased neural response within the medial prefrontal cortex, which predicts increased empathy for group members.⁷⁵ Furthermore, African American and White Americans who demonstrate high racial identification show increased cortical midline response when empathizing with members of their own racial group in painful compared with neutral scenarios (Figure 3).^72a By contrast, African Americans and White Americans who show low racial identification display increased medial temporal lobe or hippocampal response when empathizing with members of their own racial group in painful compared with neutral scenarios. These findings suggest that racial disparities in diseases that involve disruptions in functioning within medial temporal lobe structures may be more pronounced among African Americans compared with White Americans, possibly because of increased prevalence of discrimination among the minority population.

FIGURE 3—

Neural response within prefrontal and medial temporal lobe circuitry during empathy in (a) African Americans and (b) White Americans in the United States.

Note. AA = African American; CA = Caucasian American; ACC = anterior cingulate cortex; L = left; MCC = medial cingulate cortex; MPFC = medial prefrontal cortex; PCC = posterior cingulate cortex; PHG = parahippocampal gyrus; R = right.

Source. Adapted from Mathur et al.^72b Whiskers indicate 95% confidence intervals.

*P < .01; **P < .001.

Cultural values of hierarchy preference, or social dominance orientation, have also been shown to modulate neural responses of intergroup empathy. For instance, Cheon et al.^78a found that Koreans show increased left temporo-parietal junction response when viewing members of their own group in pain compared with members of another group, such as White Americans. Furthermore, this left temporo-parietal junction response was associated with increased self-reported empathy for group members because of increased cultural preference for hierarchy. Cultures characterized by social hierarchy may endorse social norms and routines that rely on conceptual understanding of people’s thoughts, feelings, and beliefs, or a theory of mind, to a greater extent compared with cultures characterized by egalitarianism that may endorse social norms that emphasize a phenomenological understanding of others, by simulating or mirroring the emotional, social, and bodily states of others. In another cross-cultural neuroimaging study, Cheon et al.^78b further found that the quality of attending to others, or “other-focusedness,” plays a key role in modulating neural response within empathic neural circuitry, such as the anterior of the cingulate cortex and anterior insula. Hence, cultural values play an important role in how the mind and brain respond to the emotions of others, particularly to their suffering or signals of distress.

Subjective social standing may also play a key role in shaping neurobiological mechanisms of emotion and social cognition. Muscatell et al.¹⁵ recently showed that both subjective and objective social economic standing are more likely to use the medial prefrontal brain regions associated with thinking about other people. Lower SES individuals are also more likely to show increased amygdala response to threatening faces. Subjective SES also modulates neural response to social status information. Individuals show increased ventral striatum response to social status information consistent with their subjective SES.¹⁸ Hence, the human brain processes social and emotional information differentially depending on both the perceived and actual SES of others.

CULTURE–GENE COEVOLUTION OF INDIVIDUALISM–COLLECTIVISM AND 5-HTTLPR

A key question to advance our understanding of population mental health disparities is the nature or origin of group differences in cultural and genetic factors that regulate psychological and neural processes underlying human behavior and well-being. Classic evolutionary theory posits that adaptive traits become more prevalent across generations through natural selection.³³ Evolutionary psychologists have further theorized that the cognitive and neural architecture of the human mind has been largely shaped by adaptive processes and reflects cortical specialization developed in response to environmental challenges.⁶¹ By contrast, culture–gene coevolutionary theory has emerged as a complementary theory that explains human behavior as a byproduct of both cultural and genetic selection, whereby humans create and maintain cultural values, practices, and beliefs, such as niches or environments that alter genetic selection and the adaptive value of behavioral traits. A particularly prominent example of culture–gene coevolution is the association between genetic selection of lactose producing alleles in cattle and genetic selection of lactose tolerance alleles in human cultures that endorse lactose consumption.⁷⁹ Within Europe, geographic regions that have increased prevalence of genes that regulate milk production in cattle also show increased prevalence of lactose tolerance genes in humans.⁷⁹

Findings from cultural neuroscience provide novel evidence of culture–gene coevolution in humans. Specifically, cultural selection of individualism–collectivism may have occurred, in part, because of genetic selection of the serotonin transporter gene.³³ Previous research has shown that environmental challenges, such as pathogen prevalence, are associated with increased collectivistic values, which may serve an “antipathogen” function, protecting geographic regions susceptible to infectious disease by encouraging social habits that minimize the likelihood of pathogen transmission.⁸⁰ Recently, we showed that nations with increased endorsement of collectivistic cultural norms also show increased prevalence of S allele carriers of the serotonin transporter gene³³ (Figure 4 ). We also found that pathogen prevalence, or the presence of infectious disease, predicts increased cultural collectivism, or emphasis on social harmony, across nations, partially because of genetic selection of the serotonin transporter gene.

FIGURE 4—

Geographical coincidence between serotonin transporter gene diversity and (a) frequency distribution of individualism-collectivism, (b) frequency distribution of S alleles of 5-HTTLPR, (c) frequency of global prevalence of anxiety, and (d) frequency of global prevalence of mood disorders.

Note. Color maps include all available published data for each variable of interest. Gray areas indicate geographical regions where no published data are available. Yellow to red color bar indicates low to high prevalence.

Source. Adapted from Chiao and Blizinsky.³³

Surprisingly, despite genetic selection of the S allele of the serotonin transporter gene, particularly in East Asian regions, epidemiological prevalence of mental health disorders, specifically anxiety and mood disorders, was lower compared with geographic regions that showed no genetic selection of the same allele.³³ Our findings further indicated that genetic selection of the S allele predicted decreased anxiety and mood disorders because of cultural selection of collectivism (Figure 5). From these findings, we suggest that there are at least 2 possible cultural neuroscience models of anxiety and mood disorders, and possibly other mental health phenomena. First, we propose a “cultural competence hypothesis,” that greater psychological well-being may result when cultural and genetic selection produce psychological and neural mechanisms that facilitate social competence within the culture. For instance, individuals who carry the S allele compared with L allele of the serotonin transporter may demonstrate social behaviors that facilitate social connection within collectivistic and individualistic cultures, respectively, thereby enhancing their ability to facilitate adaptive social behaviors within and across cultural contexts. In contrast, we propose a “cultural resilience hypothesis,” in which greater psychological well-being may result when cultural and genetic selection produce psychological and neural mechanisms that provide complementary functions. For instance, individuals who carry the S allele compared with the L allele of the serotonin transporter may demonstrate social behaviors that facilitate cultural collectivism and individualism, respectively, because of their ability to provide resilience either in psychological or physical health, within and across cultural contexts.

FIGURE 5—

Cross-nationally, greater allelic frequency of the S allele of the serotonin transporter gene is associated with reduced prevalence of anxiety and mood disorders, because of increased cultural collectivism.

Note. IND-COL = individualism-collectivism.

Source. Adapted from Chiao and Blizinsky.³³

*P <.05.

More specifically, within Eastern cultural contexts, individuals who carry the S allele compared with the L allele of the serotonin transporter may demonstrate an increased risk factor for negative effects; however, collectivistic cultural norms may provide a resilience factor, serving to buffer S allele carriers from increased exposure to or negative effects of environmental pressures.³³ By this view, cultural collectivism may confer increased resilience to anxiety and mood disorders, even within Western or multicultural contexts within the same geographic region, given the known variation of individualistic and collectivistic cultural values across individuals (e.g., cultural priming within bicultural and monocultural individuals^81,82) and groups (e.g., state-by-state variation in cultural individualism–collectivism within the United States).⁸³ Recent longitudinal evidence from within Brazil provides convergent evidence for a moderating role of the serotonin genotype on cultural effects on mental health.^84,85

Understanding the complex interplay of cultural, genetic, and environmental factors (C×G×E) that contribute to psychological well-being is at the frontier of research in cultural neuroscience. Americans, but not Koreans, show a C×G×E interaction in emotional factors that seeks out support as a function of level of emotional distress.⁸⁶ Additionally, in the United States, White Americans and Asian Americans who carry 2 copies of the G allele of the oxytocin receptor polymorphism (OXTR) rs53576 rely less on emotional suppression, whereas in Korea, Koreans rely more on emotion suppression as an emotion regulation strategy.⁸⁷ Recent neuroscience evidence suggests that the amygdala response to facial expressions in Korean women varies as a function of serotonin genotype (5-HT(2A) SNP rs6311),⁷⁵ in a manner opposite of that previously found in a Caucasian population in Europe,⁸⁸ suggesting that such C×G×E interactions may alter both psychological and neural mechanisms underlying global mental health.

OPPORTUNITIES AND CHALLENGES FOR FUTURE RESEARCH

Although the current state of cultural neuroscience research provides a novel lens into understanding population health disparities across the globe, further progress at the intersection of these research milieus relies on increasing research capacity (e.g., effective community of researchers and sufficient infrastructural research support in both the Western industrialized and developing world). We describe outstanding challenges and opportunities for building research capacity in cultural neuroscience (Table 3 ).

TABLE 3—

Challenges and Opportunities for Building Research in Cultural Neuroscience

Challenges and Opportunities
North: HICs	South: LMICs
Increasing awareness of existing researcher biases (e.g., population samples)	Providing research training and skills
Providing infrastructure or opportunities to build research collaborations with LMICs beyond existing resources	Building local ownership of theory and methods
Identifying key scientific questions that require collaboration across the North–South divide	Building institutions with training opportunities
Creating genuine, nonexploitative research partnerships	Providing access and maintenance to necessary laboratory settings and equipment
Bridging sociological gaps within the social–natural sciences that typically prevent transdisciplinary collaboration	Supporting training opportunities for junior and senior scientists abroad
Creating or adopting culturally appropriate language in theory and methods to appropriately account for phenomena in LMICs	Avoiding “brain drain” of local scientists trained abroad by creating opportunities for senior scientists to develop research and training infrastructures locally
Identifying individuals, institutions, and research networks with a long-term commitment to LMIC scientific partnerships	Creating genuine, nonexploitative research partnerships
Providing training to individuals and institutions on how to create and sustain North–South scientific partnerships	Providing access to online scientific communication, including e-mail, journals and researcher databases
Anticipating and addressing ethical issues in research specific to North–South scientific partnerships	Maintaining political stability to allow the sustainability of scientific infrastructure
	Setting realistic national scientific priorities regarding mental health disorders, and their etiology and treatment
	Identifying individuals, institutions. and research networks with a long-term commitment or willingness to foster HIC scientific partnerships
	Providing training to individuals and institutions for how to create and sustain North–South scientific partnerships
	Anticipating and addressing ethical issues in research specific to North–South scientific partnerships
Create novel scientific knowledge that uniquely addresses the etiology and treatment of mental health disorders in non-Western regions of the world	Identify key scientific questions that require collaboration across the North–South divide
Enhance existing institutions with institutes and workshops that highlight global mental health issues unique to LMICs	Create novel scientific knowledge that uniquely addresses the etiology and treatment of mental health disorders prevalent locally and regionally, in non-Western regions of the world
Partner to develop novel theory and methods in cultural neuroscience that characterize the etiology and treatment of mental health disorders locally and regionally	Develop novel theory and methods in cultural neuroscience that characterize the etiology and treatment of mental health disorders locally and regionally
Partner to develop methods in cultural neuroscience that respect local and historical traditions within the population	Develop methods in cultural neuroscience that respect local and historical traditions within the population
Create and support international training opportunities for junior and senior scientists (e.g., NSF, EAPSI, Fulbright, NIH, Fogarty)	Build national scientific infrastructure, including the creation of scientific institutions and intellectual capacity of scientists
Create and support novel funding opportunities for institutions (e.g., center, consortium, large equipment grants)	Create and broaden opportunities for institutions and individuals to provide scientific leadership locally, regionally, and internationally
Develop communication and scientific tools that enable researchers to develop novel collaborations	Enhance the overall economic and political stability of the local region
Develop tools that enable researchers to build and improve the quality and efficiency of existing collaborations	Create and support international training opportunities for junior and senior scientists (e.g., NSF EAPSI, Fulbright, NIH, Fogarty)
Expand scope and breadth of research ethics in global mental health	Create and support novel funding opportunities for institutions (e.g., center, consortium, large equipment grants)
Increase probability of scientific advance in nonglobal mental health-related research by learning from and working in a diverse scientific team	Develop communication and scientific tools that enable researchers to develop novel collaborations
	Develop tools that enable researchers to build and improve the quality and efficiency of existing collaborations
	Expand scope and breadth of research ethics in global mental health
	Increase probability of scientific advance in nonglobal mental health related research by learning from and working in a diverse scientific team

Note. EAPSI = East Asia-Pacific Summer Institute; HIC = high-income country; LMIC = low- to middle-income country; NIH = National Institutes of Health; NSF = National Science Foundation.

The research skills required by these scientists can range from knowledge of qualitative to quantitative measurement and data analytic techniques. Ideally, each member of the research team has an understanding of the theoretical questions and methodological requirements necessary for the given project; however, an expert understanding across all disciplines by all members is not necessary for a project to succeed. As is typical of large-scale team science, research projects that integrate training of junior scientists with mentoring from senior scientists from each respective discipline enriches the pedagogical value of such research and enhances the probability of success for future successful research projects by the team or by team members.

Key theoretical and methodological advances in cultural neuroscience rely heavily on large-scale team science, typically including multi-institutional, international, and interdisciplinary partnerships.^89,90 Given the sociological stratification of research training in the social and natural sciences, a typical research team conducting cultural neuroscience research may involve scientists from at least 1 discipline from social science, including anthropology and cultural psychology, and 1 discipline from natural science, including neuroscience and genetics.

There are currently 2 kinds of models for research collaborations in cultural neuroscience: individual site and multisite. The design of these models is constrained primarily by the methodological consideration in conducting neuroscience research, given that research methods in cultural and genetic science are largely mobile and unrestrained to a specific geography. Human neuroscience research, such as functional neuroimaging, typically involves heavy, stationary equipment that does not easily allow for measurement of participants outside of the existing laboratory; for ease and efficiency in study design, in individual site studies, neurobiological responses from participants are measured within individual sites. In individual site studies, researchers may conceptualize race/ethnicity as a proxy for culture and compare neurobiological or genetic responses across 2 or more racial or ethnic groups living within a shared geographic region. From a scientific perspective, the individual-site model is advantageous because it controls for measurement site as a potential confounder and can allow for merging of ethnographic and biomarker measurement in distinct local populations (e.g., hunter-gatherer tribe). However, it has a disadvantage in that such models are usually not able to measure variance in neurobiological and behavioral responses across populations because of cultural or genetic distance. From a building research perspective, the individual-site model is advantageous, in that scientific leadership and resource distribution is decided regionally or locally within nations; however, it has the disadvantage of a lack of opportunity for individuals and institutions to build long-term research partnerships across the North–South or developed or developing world divide.

By contrast, in multisite collaborations, researchers measure neurobiological and behavioral responses across sites and conceptualize culture by nationality or self-reported values. From a scientific perspective, the multisite model is advantageous because it allows for neurobiological measurement across cultural and genetically distant geographic regions. However, it has a disadvantage in that such models introduce a greater number of environmental variables into the design, making it important for the researcher to consider additional sources of genetic and environmental variance when explaining observed variation across participant groups. From a building research perspective, the multisite model is advantageous because it allows for increasing research across institutions and the North–South or developed or developing world divide, thus allowing greater research and training opportunities across geographic regions. However, the multisite model has a potential disadvantage because coordination of research and training logistics is more complex, requiring larger teams of scientists and administrators to negotiate scientific leadership and resource distribution within and across research sites in a contextually and culturally appropriate manner.

Chief among the set of research skills typically necessary to conduct cultural neuroscience studies that address questions related to global mental health include knowledge of the following:

1. anthropology or qualitative methods, such as community group interviews;

2. psychology or quantitative methods, such as behavioral surveys;

3. human neuroscience, such as functional neuroimaging or event-related potentials;

4. population or behavioral and neurogenetics, including specific functional polymorphisms and principles of evolutionary biology; and

5. epidemiology, including factors that affect local, regional, and global prevalence of mental health disorders.

This research skill set is unique in that cultural neuroscientists need both theoretical and empirical knowledge for integrating the study of cultural and genetic diversity in the production of neural and psychological processes that produce human behavior. For instance, without precise methods for quantifying culture, it is not possible to study the effects of culture on neural processes. Without knowledge of specific genetic polymorphisms that shape neural response, it is not possible to investigate how cultural variation in the genome shapes neural activity. Hence, this integrative research skill set is also applicable to researchers and scientists who need interdisciplinary knowledge for understanding how human diversity affects population health disparities.

Knowledge across these disciplines is transmitted through institutional training, typically graduate programs and individual laboratory training in public and private universities, as well as national and private research laboratories. Institutions that foster transdisciplinary training (i.e., research programs or clusters that require coursework and research opportunities in both social and natural sciences) are more likely to foster research teams that advance cultural neuroscience theory and research that meets the needs of global mental health. Research skills are also gained through access to scientific communication, including online scientific databases, research networks, and peer-reviewed journals, all of which describe research advances. Most of the institutional resources necessary for gaining training or research skills related to cultural neuroscience currently are found mostly within the North; opportunities for research training and skills exist and can be further created and maintained in the South, with special consideration to ensuring local ownership of training content and research skill transmission. Additionally, training opportunities can be provided to scientists and students from the South in the North (e.g., research workshops, conferences, institutes).

CHALLENGES TO AND OPPORTUNITIES FOR INNOVATIVE RESEARCH

In summary, there are a number of challenges and opportunities for building research in cultural neuroscience, within the North and South regions, or across the developed or developing world divide.⁹⁰ Given the direct relevance of cultural neuroscience research to meeting the key challenges faced in global mental health, it will be incumbent for scientists and institutions to find ways to overcome existing challenges and develop opportunities for enhancing the scope and sophistication of theoretical and methodological tools in cultural neuroscience research across the globe.